PROJECT SUMMARY New York State (NYS) ranks second in the nation in absolute numbers of opioid overdose deaths. From 2015- 2016, opioid overdose deaths in NYS increased by 32%, including an 88% increase in synthetic opioid-related deaths. The proposed research will develop and test a County-system Hub and Spoke Empowerment model (?CHASE?) to reduce incidence of fatal overdoses in 15 geographically and racially diverse counties in NYS that averaged 28.2 deaths per 100,000 in 2017 and meet all the UM1 RFA-DA-19-016 criteria. CHASE is a modified Hub and Spoke model that is adaptable to the unique needs of any particular county with the aim of developing a blueprint that could be applied to counties across the U.S. CHASE is a coordinated multi-system, multi-sector public health response to the opioid epidemic, directed by County Health Commissioners, and driven by robust community engagement and real-time learning based on data science and systems science. CHASE addresses structural barriers to decreasing opioid deaths by engaging underutilized county systems ?Spokes? (e.g., jails, other justice settings, emergency departments (EDs), and other health and social service settings ) will be linked to ?hubs? which will include federally qualified health care clinics, primary care settings and addiction programs. CHASE will target gaps in the opioid prevention and treatment cascade by (1) expanding number of medications for opioid use disorder (MOUD) providers and addiction expertise; (2) identifying people at risk of opioid use disorder (OUD) using evidence-based screening, brief intervention and referral tools and linking and retaining them in MOUD using peer navigation; (3) scaling up overdose education and naloxone distribution (OEND) in community settings; (4) improving access to MOUD in jails and EDs, (5) deploying evidence-based prevention programs in schools, social media and other venues; and (6) scaling up prescription monitoring and prescription take-back programs. The county leadership will work with a county community advisory board of key stakeholders to customize and calibrate the intervention components of CHASE. This calibration process will be guided by an interactive dashboard that facilitates data-driven system modelling to identify the combination of evidence-based strategies to best address specific gaps and opioid overdose trends in their county. This dashboard will also provide real-time feedback on how to improve and optimize implementation efforts. The study will employ mixed methods to rigorously identify multi-level theory- driven factors that impede or facilitate the implementation and sustainability of CHASE in each county. If effective, CHASE can be scaled up as comprehensive public health response to the opioid epidemic in counties across the U.S. This study will build on the extensive research of the multidisciplinary team on OUD and other substance use disorders, HIV, HCV and other comorbid conditions, opioid overdose prevention, pharmacology, data and system science, implementation science, and community-based participatory research and will include government investigators from NYS Department of Health.